Limited Role of Developmental Programmed Cell Death Pathways inDrosophila norpARetinal Degeneration

Abstract

We examined the role of programmed cell death (PCD) pathways in retinal degeneration caused by a mutation in the norpA gene. norpA degeneration shows morphological hallmarks of programmed cell death, specifically cytoplasmic condensation and engulfment of the dying photoreceptor cells by neighboring retinal pigment cells. However, genetic mosaic analysis of adult photoreceptors lacking rpr, hid, and grim show that these PCD inducers are not required for norpA degeneration. We showed previously that ectopic expression of either rpr or hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed by the coexpression of the baculoviral P35 caspase inhibitor. In contrast, expression of P35 does not suppress norpA retinal degeneration, although a small delay in the rate of degeneration is observed in low light-low temperature conditions. P35 does not alter the morphological characteristics of norpA cell death. Overexpression of the Drosophila inhibitor of apoptosis Diap1 or a dominant-negative form of the Dronc caspase, even when coexpressed with P35, does not dramatically alter the time course of norpA degeneration. These results establish that the pathways responsible for PCD in development do not play a major role in adult retinal degeneration caused by norpA.

Phototransduction and retinal degeneration in Drosophila

“…Despite the diversity in mechanisms underlying photoreceptor cell death in Drosophila, many of the retinal degenerations show features of apoptosis, which is reminiscent of human retinal dystrophies [31,98,234,235]. Although a lot of progress has been made over the past few years, there remain many unanswered questions regarding the mechanisms of retinal degeneration in Drosophila.…”

Molecular genetics of retinal degeneration: A Drosophila perspective

“…However, genetically removing or reducing the cell death inducers from photoreceptors including RHG fails to prevent death of norpA photoreceptors. 139 Moreover, overexpression of DIAP1 is not able to suppress degeneration, nor is the expression of a dominant negative caspase (Dronc). Thus, retinal degeneration observed in norpA is not attributed to the caspase-dependent PCD, unlike that of NinaE mutants expressing ADRP-like Rh1 rhodopsin.…”

Mutations inString/CDC25inhibit cell cycle re-entry and neurodegeneration in aDrosophilamodel of Ataxia telangiectasia

“…1). We consider these phenotypes signs of degeneration as they are observed in flies with light-induced or agerelated photoreceptor degeneration due to mutations in phototransduction pathway genes (Davidson and Steller 1998;Hsu et al 2004). In contrast, these phenotypes were not observed in GMR-GAL4, Elav-GAL4, or pATM flies, although GMR-GAL4 flies had a low rate of ommatidial defects (Figs.…”